ω-Aryl-13,14-didehydro-inter-oxa PGE compounds

ABSTRACT

This invention comprises certain analogs of the prostaglandins in which the double bond between C-13 and C-14 is replaced by a triple bond. Also provided in this invention, are novel chemical processes and novel chemical intermediates useful in the preparation of the above prostaglandin analogs. These prostaglandin analogs exhibit prostaglandin-like activity, and are accordingly useful for the same pharmacological purposes as the prostaglandins. Among these purposes are blood pressure lowering, labor induction at term, reproductive-cycle regulation, gastric antisecretory action, and the like.

The present application is a divisional application of Ser. No. 776,552,filed Mar. 7, 1977, which is a divisional application of Ser. No.657,739, filed Feb. 13, 1976, issued as U.S. Pat. No. 4,029,681 on June14, 1977.

The present invention relates to prostaglandin analogs, for which theessential material constituting disclosure therefor is incorporated byreference here from Ser. No. 657,739, filed Feb. 13,1976, now issued asU.S. Pat. No. 4,029,681.

I claim:
 1. A prostaglandin analog of the formula: ##STR1## wherein Y₁is --C.tbd.C--; wherein Z₄ is(1) --CH₂ --O--CH₂ --(CH₂)_(g) --CH₂ --,(2) --(ch₂)₂ --o--(ch₂)_(g) --CH₂ --, or (3) --(CH₂)₃ --O--(CH₂)_(g) --,Wherein g is one, 2, or 3; Wherein Z₃ is oxa or methylene; Wherein T ischloro, fluoro, trifluoromethyl, alkyl of one to 3 carbon atoms,inclusive, or alkoxy of one to 3 carbon atoms, inclusive, and s is zero,one, 2, or 3, the various T's being the same or different, with theproviso that not more than two T's are other than alkyl; Wherein M₁ is##STR2## wherein R₅ and R₆ are hydrogen or methyl, with the proviso thatone of R₅ and R₆ is methyl only when the other is hydrogen; Wherein L₁is ##STR3## wherein R₃ and R₄ are hydrogen, methyl, or fluoro, being thesame or different, with the proviso that one of R₃ and R₄ is fluoro onlywhen the other is hydrogen or fluoro and Z₃ is methylene; and Wherein R₁is hydrogen, alkyl of one to 12 carbon atoms, inclusive, cycloalkyl of 3to 10 carbon atoms, inclusive, aralkyl of 7 to 12 carbon atoms,inclusive, phenyl, phenyl substituted with one, two, or three chloro oralkyl of one to 3 carbon atoms, inclusive, or a pharmacologicallyacceptable cation.
 2. A compound according to claim 1, wherein D is##STR4##
 3. A compound according to claim 1, wherein D is ##STR5##
 4. Acompound according to claim 3, wherein Z₃ is methylene.
 5. A compoundaccording to claim 4, wherein s is zero or one and T is chloro, fluoro,or trifluoromethyl.
 6. A compound according to claim 3, wherein Z₃ isoxa.
 7. A compound according to claim 6, wherein s is zero.
 8. Acompound according to claim 6, wherein s is zero or one and T is chloro,fluoro, or trifluoromethyl.
 9. A compound according to claim 8, whereinZ₄ is --(CH₂)₃ --O--(CH₂)_(g) --.
 10. A compound according to claim 8,wherein Z₄ is --(CH₂)₂ --O--(CH₂)_(g) --CH₂ --.
 11. A compound accordingto claim 8, wherein Z₄ is --CH₂ --O--CH₂ --(CH₂)_(g) --CH₂ --.
 12. Acompound according to claim 11, wherein M₁ is ##STR6##
 13. A compoundaccording to claim 12, wherein g is one.
 14. A compound according toclaim 13, wherein R₃, R₄, R₅, and R₆ are all hydrogen. 15.15-epi-5-oxa-16-phenoxy-17,18,19,20-tetranor-13,14-didehydro-PGE₁,methyl ester, a compound according to claim
 14. 16. A compound accordingto claim 11, wherein M₁ is ##STR7##
 17. A compound according to claim16, wherein g is three.
 18. A compound according to claim 16, wherein gis one.
 19. A compound according to claim 18, wherein R₃ and R₄ are bothhydrogen.
 20. A compound according to claim 19, wherein R₅ is methyl.21.5-Oxa-16-phenoxy-17,18,19,20-tetranor-15-methyl-13,14-didehydro-PGE₁, acompound according to claim
 20. 22.5-Oxa-16-phenoxy-17,18,19,20-tetranor-15-methyl-13,14-didehydro-PGE₁,methyl ester, a compound according to claim
 20. 23. A compound accordingto claim 19, wherein R₆ is methyl. 24.5-Oxa-16-phenoxy-17,18,19,20-tetranor-13,14-didehydro-PGE₁, 15-methylether, a compound according to claim
 23. 25.5-Oxa-16-phenoxy-17,18,19,20-tetranor-13,14-didehydro-PGE₁, methylester, 15-methyl ether, a compound according to claim
 23. 26. A compoundaccording to claim 19, wherein R₅ and R₆ are both hydrogen. 27.5-Oxa-16-phenoxy-17,18,19,20-tetranor-13,14-didehydro-PGE₁, a compoundaccording to claim
 26. 28.5-Oxa-16-phenoxy-17,18,19,20-tetranor-13,14-didehydro-PGE₁, methylester, a compound according to claim
 26. 29. A compound according toclaim 18, wherein at least one of R₃ and R₄ is methyl.
 30. A compoundaccording to claim 29, wherein R₃ and R₄ are both methyl.
 31. A compoundaccording to claim 30, wherein R₅ is methyl. 32.5-Oxa-16-phenoxy-18,19,20-trinor-15,16-dimethyl-13,14-didehydro-PGE₁,methyl ester, a compound according to claim
 31. 33. A compound accordingto claim 30, wherein R₆ is methyl. 34.5-Oxa-16-phenoxy-18,19,20-trinor-16-methyl-13,14-didehydro-PGE₁, methylester, 15-methyl ether, a compound according to claim
 33. 35. A compoundaccording to claim 30, wherein R₅ and R₆ are both hydrogen. 36.5-Oxa-16-phenoxy-18,19,20-trinor-16-methyl-13,14-didehydro-PGE₁, acompound according to claim
 35. 37.5-Oxa-16-phenoxy-18,19,20-trinor-16-methyl-13,14-didehydro-PGE₁, methylester, a compound according to claim 35.